The present disclosure relates generally to mechanical conditioning of engineered tissues and, more particularly, systems and methods for conditioning or controlling processing of microtissues.
Engineered biological tissues provide the potential for options beyond the traditional treatments, for example, when testing drugs in development, and when performing tissue and organ repair. In addition, these tissues allow for the study of the organization and mechanical and biological function of model multicellular constructs. Static and dynamic mechanical conditioning during the engineering process have been found to enhance tissue structure, mechanical strength, and overall functionality. Mechanical conditioning of these engineered tissues traditionally requires the use of centimeter scale tissue samples and potentially complex bioreactor systems. The large scale of the tissues sets a limit to the imaging which can be performed on the tissue and the ability for pharmacological treatments to diffuse throughout.
Current cutting edge methods of tissue engineering range from bioreactors to 3D printing. The majority of these methods, however, use relatively large amounts of reagents and do not condition the tissue as it matures. The expense of certain reagents and the rarity of certain cell lines necessitate a method for high-throughput tissue engineering that uses few materials. Furthermore, conditioning is an important step that contributes to the tissues' ultimate mechanical integrity.
A range of microengineered devices fabricated from soft materials, such as poly(dimethylsiloxane) (PDMS), have been developed that can measure the force generation (contractility) of model tissues of the millimeter and sub-millimeter scales during the process of tissue conditioning. In these devices, cells and extracellular matrix self-assemble under the contractile action of the cells into tissue constructs suspended between a pair of flexible vertical cantilevers, whose deflection reports the net contractile force generated by the cells in the tissue. These microtissue strain gauges have enabled the study of contractility in a range of model tissues, involving fibroblasts, airway smooth muscle cells, and cardiomyocytes.
The capability of such force measuring devices can be greatly expanded by enabling actuation of the microtissues, as this can allow further exploration of the properties of such tissue constructs. In addition, actuation allows for analysis of both acute and long-term response to mechanical conditioning of the specific tissues. It would be desirable to have a system and method that allows for further actuation of tissue constructs during a conditioning and measuring process.